ABSTRACT The Dry Eye Assessment and Management (DREAM) Study Research Group successfully completed a large-scale multi-center placebo-controlled clinical trial (N=535), sponsored by the National Eye Institute, to evaluate the effect of omega-3 fatty acid supplementation for the treatment of dry eye disease (DED). During the trial, the DREAM Study collected comprehensive data over the course of 12-months of follow-up through clinical assessment of dry eye signs, symptoms, laboratory assessment of ocular surface biomarkers and systemic antibodies, clinical meibomian assessment, reading center evaluation of meibomian gland features, and standard interview of patients on medical history and medication use. The proposed project will perform secondary analyses of these rich and unique data to achieve the following goals: (1) To classify dry eye disease into subtypes through latent class analysis of the dry eye signs, symptoms, biomarkers and meibomian gland assessments, and to evaluate the effect of omega-3 fatty acid supplementation in each subtype of dry eye disease. (2) To determine the association of systemic diseases (thyroid disease, diabetes, depression, rosacea) and use of systemic medications with the severity of dry eye disease at baseline and its longitudinal change over time. (3) To determine the cross-sectional and longitudinal correlations among inflammatory markers (cytokines, HLA-DR and other cellular markers, MMP-9) and their longitudinal change over time. (4) To evaluate the cross-sectional and longitudinal associations of results from point-of-care dry eye tests (osmolarity test, MMP-9 test, ocular surface imaging including meibomian gland assessments) with traditional dry eye signs and symptoms. The proposed secondary analyses of rich and unique data from the DREAM study will lead us to better classification of the heterogeneity of dry eye disease, the identification of associated risk factors for dry eye disease severity, improved understanding of the role of inflammation in DED, and the utility of point-of-care tests for DED. Thus, this project has great potential to lead to better diagnosis, characterization and management of patients with dry eye disease. Insight on the pathophysiological of DED from these analyses may lead to the development of new treatments of DED. The large sample size of well-characterized trial participants, high quality of longitudinal datasets, as well as the rich experience and high productivity of the investigators support the feasibility and likelihood of high yield of the proposed project.